TY - JOUR
T1 - Trombospondin-2 is essential for myocardial matrix integrity: increased expression identifies failure-prone cardiac hypertrophy
AU - Schroen, B.
AU - Heymans, S.
AU - Sharma, U.
AU - Blankesteijn, W. Matthijs
AU - Pokharel, S.
AU - Cleutjens, J.P.M.
AU - Porter, G.
AU - Evelo, C.T.A.
AU - Duisters, R.
AU - Leeuwen, van, R.E.W.
AU - Janssen, B.J.A.
AU - Debets, J.J.M.
AU - Smits, J.F.M.
AU - Daemen, M.J.A.P.
AU - Crijns, H.J.G.M.
AU - Bornstein, P.
AU - Pinto, Y.
PY - 2004
Y1 - 2004
N2 - Cardiac hypertrophy can lead to heart failure (HF), but it is unpredictable which hypertrophied myocardium will progress to HF. We surmised that apart from hypertrophy-related genes, failure-related genes are expressed before the onset of failure, permitting mol. prediction of HF. Hearts from hypertensive homozygous renin-overexpressing (Ren-2) rats that had progressed to early HF were compared by microarray anal. to Ren-2 rats that had remained compensated. To identify which HF-related genes preceded failure, cardiac biopsy specimens were taken during compensated hypertrophy and we then monitored whether the rat progressed to HF or remained compensated. Among 48 genes overexpressed in failing hearts, we focused on thrombospondin-2 (TSP2). TSP2 was selectively overexpressed only in biopsy specimens from rats that later progressed to HF. Moreover, expression of TSP2 was increased in human hypertrophied hearts with decreased (0.190.01) vs. normal ejection fraction (0.110.03 [arbitrary units]; P
AB - Cardiac hypertrophy can lead to heart failure (HF), but it is unpredictable which hypertrophied myocardium will progress to HF. We surmised that apart from hypertrophy-related genes, failure-related genes are expressed before the onset of failure, permitting mol. prediction of HF. Hearts from hypertensive homozygous renin-overexpressing (Ren-2) rats that had progressed to early HF were compared by microarray anal. to Ren-2 rats that had remained compensated. To identify which HF-related genes preceded failure, cardiac biopsy specimens were taken during compensated hypertrophy and we then monitored whether the rat progressed to HF or remained compensated. Among 48 genes overexpressed in failing hearts, we focused on thrombospondin-2 (TSP2). TSP2 was selectively overexpressed only in biopsy specimens from rats that later progressed to HF. Moreover, expression of TSP2 was increased in human hypertrophied hearts with decreased (0.190.01) vs. normal ejection fraction (0.110.03 [arbitrary units]; P
U2 - 10.1161/01.RES.0000141019.20332.3e
DO - 10.1161/01.RES.0000141019.20332.3e
M3 - Article
SN - 0009-7330
VL - 95
SP - 506
EP - 514
JO - Circulation Research
JF - Circulation Research
IS - 5
ER -